PROJECT SUMMARY/ABSTRACT Adolescents tend to consume alcohol less often but at higher volumes than adults do, a pattern referred to as binge drinking. Because adolescence is a critical period for brain development, excessive exposure to alcohol is particularly concerning. For example, during adolescence the prefrontal cortex (PFC) GABAergic system matures from the pre-adolescent state of great excitation to inhibition to reduced, adult-like proportions. This GABAergic development is disrupted by exposure to alcohol, a GABA agonist, resulting in increased excitatory/inhibitory (E/I) balance in the PFC that persists into adulthood. One facet of executive function that is reliant on the PFC and that published data suggest is impacted by adolescent binge drinking is behavioral flexibility, which describes an individual?s ability to adjust their behavior to changing environmental circumstances. Indeed, reduced PFC GABA has been associated with both adolescent binge alcohol exposure and impairments in behavioral flexibility, but no studies to date have evaluated whether reduced GABA, or more generally, a skewed E/I balance, mediates the association between adolescent alcohol exposure and behavioral inflexibility in humans. Based on available evidence, we hypothesize that adolescent binge drinking increases the E/I balance of the PFC. Thus, the proposed study will first assess group differences in E/I balance amongst adults with and without a history of adolescent binge drinking using a recently described method in which E/I balance can be derived from the slope of the brain?s electroencephalographic (EEG) power spectrum (Aim 1). Further, we hypothesize that adults with a history of adolescent binge drinking will exhibit reduced behavioral flexibility, and that E/I balance will mediate this relationship (Aim 2). To test this, we will utilize the Hidden Association Between Images Task to assess habitual responding, a metric of inflexible behavior. To further test the relationship between E/I balance and behavioral flexibility, we will assess whether bilateral transcranial alternating current stimulation (tACS) of the PFC, which modulates the E/I balance of stimulated brain regions, alters performance on this task-based measure of behavioral flexibility (Aim 3). We hypothesize that PFC stimulation which increases the E/I balance of the brain will impair behavioral flexibility. Together, this proposed research will provide new information regarding persistent neural and behavioral changes associated with adolescent binge drinking. Given evidence that early alcohol use is associated with elevated lifetime prevalence of substance use disorders, and that behavioral inflexibility and disruptions in E/I balance are present in adults with substance use disorders, insight into these relationships could provide a mechanistic link between early alcohol use and this elevated risk and could thereby aid in the development of novel therapeutic targets.